INSR [The Human Chemical-Genetic Interaction Map Project]

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======= INSR =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: INSR
  * **<color #00a2e8>Official Name</color>**: insulin receptor
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3643|3643]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P06213|P06213]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=INSR&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20INSR|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/147670|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src- homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti- apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K- AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. {ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase|
|Pkinase Tyr|
|Furin-like|
|Recep L domain|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|insulin-activated receptor activity|
|PTB domain binding|
|transformation of host cell by virus|
|nuclear lumen|
|insulin receptor complex|
|insulin binding|
|exocrine pancreas development|
|insulin-like growth factor II binding|
|positive regulation of respiratory burst|
|neuron projection maintenance|
|dendritic spine maintenance|
|insulin receptor substrate binding|
|insulin-like growth factor I binding|
|regulation of female gonad development|
|cargo receptor activity|
|male sex determination|
|insulin-like growth factor receptor binding|
|positive regulation of glycogen biosynthetic process|
|regulation of respiratory burst|
|positive regulation of glycogen metabolic process|
|regulation of gonad development|
|phosphatidylinositol 3-kinase binding|
|amyloid-beta clearance|
|sex determination|
|positive regulation of glycolytic process|
|positive regulation of meiotic cell cycle|
|adrenal gland development|
|neuronal cell body membrane|
|dendrite membrane|
|regulation of glycogen biosynthetic process|
|regulation of glucan biosynthetic process|
|dendritic spine organization|
|modulation by virus of host morphology or physiology|
|protein heterotetramerization|
|peptidyl-tyrosine autophosphorylation|
|activation of protein kinase B activity|
|regulation of glycogen metabolic process|
|regulation of polysaccharide biosynthetic process|
|positive regulation of protein complex disassembly|
|positive regulation of glucose import|
|positive regulation of glucose metabolic process|
|positive regulation of nitric oxide biosynthetic process|
|neuron projection organization|
|positive regulation of nitric oxide metabolic process|
|modification by symbiont of host morphology or physiology|
|positive regulation of glucose transmembrane transport|
|regulation of polysaccharide metabolic process|
|exocrine system development|
|positive regulation of ATP metabolic process|
|positive regulation of nucleotide metabolic process|
|positive regulation of purine nucleotide metabolic process|
|cellular component maintenance|
|regulation of meiotic cell cycle|
|positive regulation of reactive oxygen species biosynthetic process|
|positive regulation of mitotic nuclear division|
|regulation of glucose import|
|transmembrane receptor protein tyrosine kinase activity|
|regulation of nitric oxide biosynthetic process|
|positive regulation of cellular carbohydrate metabolic process|
|positive regulation of nuclear division|
|pancreas development|
|regulation of glucose transmembrane transport|
|caveola|
|positive regulation of reproductive process|
|regulation of glycolytic process|
|positive regulation of carbohydrate metabolic process|
|amyloid-beta binding|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|regulation of reactive oxygen species biosynthetic process|
|regulation of carbohydrate catabolic process|
|insulin receptor signaling pathway|
|postsynapse organization|
|protein tyrosine kinase activity|
|regulation of carbohydrate biosynthetic process|
|positive regulation of reactive oxygen species metabolic process|
|protein heterooligomerization|
|modification of morphology or physiology of other organism involved in symbiotic interaction|
|regulation of glucose metabolic process|
|regulation of protein complex disassembly|
|regulation of purine nucleotide metabolic process|
|memory|
|regulation of nucleotide metabolic process|
|regulation of phosphatidylinositol 3-kinase signaling|
|regulation of ATP metabolic process|
|endocrine system development|
|regulation of embryonic development|
|male gonad development|
|development of primary male sexual characteristics|
|positive regulation of small molecule metabolic process|
|regulation of cellular carbohydrate metabolic process|
|digestive system development|
|peptidyl-tyrosine phosphorylation|
|learning|
|peptidyl-tyrosine modification|
|protein tetramerization|
|positive regulation of mitotic cell cycle|
|activation of MAPK activity|
|modification of morphology or physiology of other organism|
|male sex differentiation|
|interaction with host|
|regulation of generation of precursor metabolites and energy|
|regulation of reproductive process|
|cellular response to insulin stimulus|
|positive regulation of protein kinase B signaling|
|regulation of mitotic nuclear division|
|positive regulation of developmental growth|
|regulation of reactive oxygen species metabolic process|
|nuclear envelope|
|glucose homeostasis|
|carbohydrate homeostasis|
|regulation of nuclear division|
|protein autophosphorylation|
|positive regulation of transmembrane transport|
|receptor complex|
|regulation of carbohydrate metabolic process|
|gonad development|
|endosome membrane|
|development of primary sexual characteristics|
|regulation of protein kinase B signaling|
|response to insulin|
|receptor-mediated endocytosis|
|protein domain specific binding|
|heart morphogenesis|
|positive regulation of growth|
|learning or memory|
|positive regulation of MAP kinase activity|
|sex differentiation|
|protein-containing complex binding|
|cellular response to peptide hormone stimulus|
|synapse organization|
|positive regulation of cell cycle process|
|axon|
|cognition|
|cellular response to peptide|
|activation of protein kinase activity|
|regulation of developmental growth|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of neurotransmitter levels|
|positive regulation of cellular catabolic process|
|positive regulation of cell cycle|
|GTP binding|
|response to peptide hormone|
|external side of plasma membrane|
|gland development|
|epidermis development|
|reproductive structure development|
|regulation of small molecule metabolic process|
|reproductive system development|
|positive regulation of catabolic process|
|response to peptide|
|carbohydrate metabolic process|
|cellular response to growth factor stimulus|
|positive regulation of cell migration|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|protein complex oligomerization|
|positive regulation of cell motility|
|heart development|
|response to growth factor|
|positive regulation of protein kinase activity|
|positive regulation of cellular component movement|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|endocytosis|
|regulation of transmembrane transport|
|behavior|
|positive regulation of kinase activity|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|positive regulation of organelle organization|
|regulation of mitotic cell cycle|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|developmental process involved in reproduction|
|regulation of growth|
|import into cell|
|viral process|
|enzyme linked receptor protein signaling pathway|
|regulation of MAPK cascade|
|regulation of cell cycle process|
|symbiotic process|
|regulation of protein kinase activity|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|regulation of cell migration|
|circulatory system development|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|animal organ morphogenesis|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of locomotion|
|positive regulation of transport|
|regulation of catabolic process|
|regulation of cellular component movement|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|response to nitrogen compound|
|chemical homeostasis|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|cell projection organization|
|regulation of cell cycle|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|phosphorylation|
|regulation of organelle organization|
|G protein-coupled receptor signaling pathway|
|positive regulation of developmental process|
|nervous system process|
|integral component of plasma membrane|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|positive regulation of signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|membrane|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp123|GSK-LSD1 10μM R03 exp123]]|-1.83|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|1/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 15167
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.52 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='INSR Expression in NALM6 Cells: 7.52'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>